Posttraumatic Stress Disorder (PTSD)1 is a debilitating disorder that develops in some individuals who have been exposed to psychological trauma. Functional neuroimaging studies have mapped out a functional neuro-circuitry of PTSD 2. Three interconnected brain regions have consistently shown abnormal patterns of activity in this disorder 3: the amygdala, which is involved with processing of emotionally-salient stimuli; the medial prefrontal cortex (mPFC, a functionally heterogeneous region that includes the anterior cingulate cortex, the subcallosal cortex, and the medial frontal gyrus) which plays a role in modulation of affect; and the hippocampus, which is involved with memory encoding and retrieval. Auditory presentation of personalized trauma narratives during functional neuroimaging has proven useful in investigating PTSD-specific abnormalities in neural function (for a review, see 4). A common finding in this line of research is reduced mPFC response to trauma-related versus neutral scripts in individuals with PTSD 5–10.
Selective serotonin reuptake inhibitors (SSRIs), including paroxetine, have been shown to be effective in the treatment of PTSD symptoms 11, 12; however, the neural mechanisms of treatment efficacy in PTSD have not been fully established. A few studies have provided some insights into these mechanisms. Seedat and colleagues (2004) treated 11 adults with PTSD (related to different traumatic events) with citalopram for 8 weeks, conducting SPECT imaging before and after treatment; the authors found significant correlations between increases in activity in regions of the mPFC and symptom reductions, as well as decreased left medial temporal activity with treatment 13. In a case report study of a war torture victim with PTSD, Fernandez and colleagues (2001) presented war-related sounds to the patient during PET imaging; this was done both before and after 6-month treatment with fluoxetine. The authors found increased regional cerebral blood flow in various frontal regions of the brain (including the orbitofrontal cortex, prefrontal cortex, and inferior frontal cortex) during imaging, as well as a 48% decrease in symptoms, following fluoxetine treatment 14.
A third treatment study examined changes in brain function within a group of individuals with different anxiety disorders, including obsessive-compulsive disorder (OCD), PTSD, social phobia, and generalized anxiety disorder, grouped together 15. Interestingly, this study revealed decreased activity in some medial frontal regions following treatment; however, given that the authors studied a heterogeneous group of anxious participants, these findings may have limited applicability to PTSD. Individuals with disorders such as OCD have historically shown increased metabolism in medial prefrontal brain regions, while individuals with PTSD have shown an opposite pattern of activity in the mPFC 16.
In sum, functional neuroimaging studies using script-driven imagery have been useful in identifying atypical patterns of neural processing in PTSD, and SSRIs have proven effective in treating the clinical symptoms of PTSD. However, few studies have combined these methods to examine the effects of psychopharmacological treatment on brain function in PTSD, which would provide valuable insights toward understanding neural mechanisms of treatment in this disorder. Thus, the purpose of this pilot study was to assess the effects of the SSRI paroxetine on neural responses to traumatic memories in patients with PTSD through PET imaging; we hypothesized that paroxetine treatment would be associated with increased function in medial frontal regions of the brain, and that these associations would not be found in placebo-treated individuals.